The use of bioresorbable polymers for implantation in living tissue has steadily increased over the last few decades. Medical applications of such polymers include absorbable sutures, intraosseous implants and slow-release drug delivery systems.
More recently, their use has been extended to microtubular tissue regeneration guidance channels. For example, bioresorbable materials have been used in the repair of injured nerves. Nerves with severed axons, but intact somas, may retain the capability of regrowing from the proximal stump to reconnect distally. Structures have been fabricated that serve as conduits for the regrowth and reconnection of severed nerves. After accomplishing their function, these guides gradually disappear from the host.
To be effective, these devices, commonly known as nerve channels, nerve guidance channels, nerve guidance tubes, nerve guides, or nerve tubes, must be made from materials that meet a wide range of biological and physicochemical prerequisites. The material must be bioresorbable, nontoxic, noncarcinogenic, nonantigenic, and must demonstrate favorable mechanical properties such as flexibility, suturability, and amenability to custom fabrication.
Further, it has been recently appreciated that these materials also must be capable of supporting cellular growth, to the extent that they actually exert a "neurotropic" effect. After exerting such an effect, they must also retain structural integrity to the extent necessary to maximize the number of axons reaching the distal stump to restore nerve function. This requires guidance channel biodegradation/resorption rates compatible with axon growth rates.
Examples of absorbable materials used in nerve repair include collagen as disclosed by D. G. Kline and G. J. Hayes, "The Use of a Resorbable Wrapper for Peripheral Nerve Repair, Experimental Studies in Chimpanzees", J. Neurosurgery 21, 737 (1964). However, one of the major disadvantages inherent with collagenous materials is their potential antigenicity.
Two related patents, U.S. Pat. Nos. 4,033,938 and 3,960,152, disclose bioabsorbable polymers of unsymmetrically substituted 1,4-dioxane-2,5-diones which are broadly stated to be useful as tubes or sheets for surgical repair such as nerve and tendon splicing. A similar disclosure in U.S. Pat. No. 4,074,366 relates to poly(N-acetyl-D-glucosamine), i.e. chitin.
Other biodegradable polymers of particular interest for medical implantation purposes are homopolymers and copolymers of the alpha-hydroxy carboxylic acids, glycolic acid and lactic acid. These materials undergo hydrolytic scission to form metabolites normal to the body, which are therefore amenable to resorption.
A biodegradable polyglactin suture mesh shaped as a tube around a nerve defect to serve as a framework for proliferating cells has been reported in Muscle and Nerve 5, 54-57 (1982). However, less than satisfactory results were achieved in that some of the regenerating axons gained access to the meshes of the polyglactin tube causing the formation of minifascicles. A nerve cuff in the form of a smooth, rigid tube has also been fabricated from a copolymer of lactic and glycolic acids [The Hand 10, (3) 259 (1978)].
U.S. Pat. No. 4,481,353 discloses a bioresorbable polyester terpolymer that also includes an alpha-hydroxy carboxylic acid in conjunction with Krebs cycle dicarboxylic acids and aliphatic diols. These polyesters are useful in fabricating nerve guidance channels as well as other surgical articles such as sutures and ligatures.
Regenerated nerves have also been successfully obtained with nerve guides prepared from the homopolymer poly(DL-lactic acid), as measured by myelinated axon counts. The polymers used were obtained commercially, and had a weight average molecular weight of approximately 68,000, which was fractionated to a maximum weight average molecular weight of 113,000. In some cases, a bioresorbable plasticizer was added to impart flexibility and suturability. Studies conducted with a transected rat optic nerve using the nerve guide have shown that the formation of a cable is induced. The cable is composed of fibroblasts, macrophages, astrocytes, oligodendrocytes, collagen, Schwann cells, a connective tissue sheath and numerous blood vessels and myelinated and unmyelinated axons. Transactions of the American Society of Artificial Internal Organs, Vol. 29 (1983) pp. 307-313. Results with similar nerve guides, reported to have an weight average molecular weight of 100,000, are disclosed in Plastic Reconstructive Surgery 62, 173 (1984).
However, the art has yet to disclose or suggest the selective use of an alpha-hydroxy carboxylic homopolymer or copolymer in a critical range of molecular weight for implantation into living tissue.